Microglia Diversity in Health and Multiple Sclerosis.

Multiple Sclerosis (MS) is a neurodegenerative disease characterized by multiple focal lesions, ongoing demyelination and, for most people, a lack of remyelination. MS lesions are enriched with monocyte-derived macrophages and brain-resident microglia that, together, are likely responsible for much of the immune-mediated neurotoxicity. However, microglia and macrophage also have documented neuroprotective and regenerative roles, suggesting a potential diversity in their functions. Linked with microglial functional diversity, they take on diverse phenotypes developmentally, regionally and across disease conditions. Advances in technologies such as single-cell RNA sequencing and mass cytometry of immune cells has led to dramatic developments in understanding the phenotypic changes of microglia and macrophages. This review highlights the origins of microglia, their heterogeneity throughout normal ageing and their contribution to pathology and repair, with a specific focus on autoimmunity and MS. As phenotype dictates function, the emerging heterogeneity of microglia and macrophage populations in MS offers new insights into the potential immune mechanisms that result in inflammation and regeneration

Optical detection of distal lung enzyme activity in human inflammatory lung disease.

Objective and Impact Statement. There is a need to develop platforms delineating inflammatory biology of the distal human lung. We describe a platform technology approach to detect in situ enzyme activity and observe drug inhibition in the distal human lung using a combination of matrix metalloproteinase (MMP) optical reporters, fibered confocal fluorescence microscopy (FCFM), and a bespoke delivery device. Introduction. The development of new therapeutic agents is hindered by the lack of in vivo in situ experimental methodologies that can rapidly evaluate the biological activity or drug-target engagement in patients. Methods. We optimised a novel highly quenched optical molecular reporter of enzyme activity (FIB One) and developed a translational pathway for in-human assessment. Results. We demonstrate the specificity for matrix metalloproteases (MMPs) 2, 9, and 13 and probe dequenching within physiological levels of MMPs and feasibility of imaging within whole lung models in preclinical settings. Subsequently, in a first-in-human exploratory experimental medicine study of patients with fibroproliferative lung disease, we demonstrate, through FCFM, the MMP activity in the alveolar space measured through FIB One fluorescence increase (with pharmacological inhibition). Conclusion. This translational in situ approach enables a new methodology to demonstrate active drug target effects of the distal lung and consequently may inform therapeutic drug development pathways

Hydrogen generation for use in fuel cells -- wind or natural gas?

This IQP covers the use of hydrogen as a fuel for the transportation infrastructure of the future. Specifically, it focuses on sources of energy for the generation of hydrogen. Ultimately, the conclusion is drawn that wind is superior to natural gas for this purpose. This conclusion is based on financial, environmental, and safety criteria. Much of the paper is devoted to the specifics of how eIectrical energy is generated from wind and how to optimally construct an electrical generation facility for the production of hydrogen

Remote computer data acquisition for satellite

The purpose of this project was to continue the design and construction of the sensor subsystem for a prototype nanosatellite (NANOSAT) called the Powder Metallurgy and Navigation Satellite (PANSAT). Every satellite has a subsystem that is responsible for the Health and Safety of the satellite. The sensor subsystem is accountable for monitoring other subsystems and their components to make sure they are operating properly. The main requirements for the sensor subsystem are listed below: -Monitor the temperatures of satellite subsystems. -Monitor the voltages of satellite subsystems. -Monitor the current of satellite subsystems. -Monitor the magnetic field of the earth in Low Earth Orbit